The objectives of this proposal are to prepare by chemical synthesis, analogues of the triostins and quinomycins, which are a group of bicyclic depsipeptide antibiotics. Selected triostin analogues will be prepared and their binding to DNA determined. Disulfide contraction methods will be applied to prepare quinomycin analogues possessing a sulfide cross-bridge. The preparation of the dithioacetal dipeptide common to the quinomycins will be investigated. Model studies will be carried out for elaboration of the peptide portion of the quinomycin antibiotics from lanthionine precursors. The synthetic analogues will be evaluated for binding to DNA and for antitumor activity.